The synaptic properties of excitatory connections between neurons in the visual cortex and in pathways between the lateral geniculate nucleus (LGN) and cortex are not well understood. The nature of these connections defines the responses that cells make to visual stimuli. The aim of this proposal is to characterize the neurotransmitters, receptors and synaptic mechanisms that are active in these pathways. A monolayer tissue culture preparation will be used in which neurons are identified on the basis of prior retrograde labelling in vivo. Synaptic connections will be investigated by recording from identified driver/follower cell pairs in culture. The input from LGN to primary visual cortex, and the corresponding recurrent connection will be studied in mixed cultures of LGN and cortical neurons. In cortex excitatory synaptic responses involve both the NMDA and non-NMDA types of glutamate receptors; the nonNMDA receptors appear to be responsible for fast synaptic responses, while the NMDA receptors are responsible for slow responses and synaptic plasticity. The distribution of these two receptor types will be determined on dendrites of identified neurons, both in long term cultures and preparations of freshly dissociated cells. The relationship of the observed receptor distributions to synaptic sites will be investigated. Long-term potentiation, as a model for cortical plasticity, will be studied in driver/follower pairs of identified neurons in tissue culture. The goal is to identify the cell types and synaptic mechanisms involved in synaptic reorganization in cortex. The proposed experiments will extend our understanding of the synaptic processes that underlie the generation and modification of response properties of neurons in the visual cortex and lateral geniculate nucleus, including the long term changes in function associated with visual learning with amblyopia.